Most popular electronic devices have evolved from the first vacuum tube: the first electronic logic gate. Now there are more than twenty million logic gates functioning in the CPU of any PC. Electronic systems are built by integrating several basic components and several basic modules composed of those components. Logic gates and digital encoders are examples of basic components for electronic systems that perform digital operations, if given one or more logic input(s), and produce a single logic output. For example, given a logic gate having an input of two variables, there are sixteen possible algebraic functions; one simple structure, comprised of four NOR gates, can carry out all sixteen logic operations. Accordingly, this structure is called a universal logic gate (ULG), and it can be used in almost any situation. As a non-limiting example, an ULG can be used for a comparison of frequencies when developing filters in communication, or in more mechanical settings when using choppers and inverters which compare input and output currents to determine modulating indexes. Thus, a controlling system that may be formed with the help of these basic electronic components is needed.
Fluidics are an analog counterpart of electronic computing; for example, water interrogator and other sophisticated fluidic functions were already realized in 1970. Bottlenecks in miniaturization restricted further development of fluidics, resulting in the decline of this computing branch. By using photolithography techniques, especially the soft-lithography technique, fluid channels in sub-millimeter size, even nanometer, are now realized. Accordingly, microfluidic/nanofluidic chips, having a plurality of channels with the size in the range of micrometers or nanometers, are useful as “labs on a chip” and may be used in chemical reaction and biological analysis, including, for new chemical generation, enzymatic analysis, DNA analysis, proteomics, etc. Conventional operations such as sample preparation, pre-treatment and assay detection may be integrated onto a single chip.
Droplet-based microfluidics involves the generation, detection and manipulation (fission, fusion and sorting) of discrete droplets inside micro-devices. Droplets with small volumes can be used for high throughput chemical reaction and single cell manipulation in chemical and biological application. A “lab on a chip” utilizing droplets is a desired apparatus for medical and biological applications, especially for use in Point-of-Care (POC) and “outdoor testing,” and particularly in developing countries. Existing conventional equipment has many disadvantages, such as high power consumption, heavy electrical load, and environment dependence, and the “lab on a chip” concept helps address these disadvantages.
Scientists have endeavored to reinvent the near-legendary logic gate component in other systems: some binary logic functions have been successfully mimicked by fluidic diodes, microelectrochemical logic; see for example [NPL 27], and conducting-polymer-coated micro-electrode arrays; see for example [NPL 24]. In microfluidic domains, researchers have scrutinized both kinetic fluid regulation; see for example [NPL 9], [NPL 16], [NPL 19] and static geographical stream manipulation; see for example [NPL 5], [NPL 11], [NPL 14] and [NPL 25] as possible solutions. Simple logic devices such as the AND gate, OR gate, the static fluid transistor and the oscillator are some of the achievements.
Existing devices are problematic in their reliance on complex structures or exterior supporting components. They are limited in that they entail either bulky peripheral equipment for round-trip manipulation, or have complicated 3D micro-structures. Moreover, they are confined by the soft-lithographic technique with which they are formed; designed within pre-shaped architectures for distinct tasks, they have no re-programmability or cascadability.
For example, [PTL 1] describes a system containing high or low pressure sources, which includes a pump coupled to a reservoir through unidirectional valves. It may also include devices that perform analog functions such as switching regulator. In [PTL 2], the logic function in fluid is achieved by structure design to change the pressure and thus the flow direction. Similarly, in [PTL 3], devices are based on the principle of minimum energy interfaces formed between the two fluid phases enclosed inside precise channel geometries.
[PTL 4] describes an operating tool that uses programmed fluid logic provided by use of flow paths including pre-determined spaced ports and varying orifice sizes to provide discrete pressures and fluid flow rates upon pressure differential sensitive devices, such as a membrane or piston, in operative communication with an operative sleeve to manipulate one or more secondary tools, and/or to perform a service.
[PTL 5] describes a microfluidic processor with integrated active elements for handling process media, the active elements act by changes in their volume, swelling degree, material composition, their strength and/or viscosity. The procedures to be performed are (pre-)defined by the constructive configuration of the microfluidic processor by an appropriate logic connection of the individual active elements defined in their function, by the sequence of the temporal activation of the individual elements, and with respect to their processing speed and their precision. The process is enabled by action of a substantially non-directional collectively acting environmental parameter, in particular, the presence of a solvent or environmental temperature or both.
In the “lab on a chip” system, the electronic signal is needed for controlling the fluid and biological analysis through a liquid-electronic information interface. In microfluidic chips, high throughput sample screening and information processing may be achieved. As a result, high density control unions, valves, and mixers, are required. Examples of such devices are described in [NPL 9] and [NPL 19]. Despite typically needing supporting off-chip macro-scale solenoid arrays controlled by peripheral equipment, on-chip control components have attracted enormous scrutiny because of their scalability and cascadability.
Discussions of digital microfluidics (DMF) are usually confined to the context of electrowetting-on-dielectric (EWOD) fluid control systems; see for example [NPL 1] and [NPL 8], which is thought to be the most promising technique to realize digital microfluidics; see for example [NPL 17]. Indeed, among proposed on-chip controlling schemes, EWOD, where a computer is used to control droplet movement, is well-known for fine control of “digitalized” droplets. Every single step of droplet movement is well defined, in an electronic approach; see for example [NPL 8], [NPL 13], [NPL 15], [NPL 18]. Despite this, the logic operation is actually conducted by a peripheral computer system, and droplets respond passively to control signals. With EWOD systems, the paradigm for pure fluid/droplet logic, in which the fluid responds only to droplet (fluid) inputs, has somehow been neglected. The fluidic output does not respond to and is not in response to fluidic input, but to computer order. Thus, EWOD's pre-defined round trip control scheme indicates its “electronic” instead of “fluidic” nature, and diminishes its flexibility and application as a true real digitalized microfluidic device akin to a computer.
Other works have been done in pure fluidic logic, for example, geometry decided bubble logic and continuous phase logic; see for example [NPL 22]. The above techniques are usually based on pressure resistance, which results in a specific designed channel configuration for each logic operation, and thus the inevitable amplified perturbation in fluidic system usually occurs. Indeed, previous ‘solutions’ can be characterized as posing complicated 3D architecture, and require specific designs for each logic function. See citation listing, especially for example, [NPL 14], [NPL 11] and [NPL 25].
3D produces many practical problems in chip-integration. Firstly, three dimensional connections provide fluid turbulence, which generate unexpected drop merge or flow disturbance, leading to message drop-out. Secondly, to realize a real logic processor, all of the logic functions need to be integrated to realize cascading information processes. Technically, a 3D microfluidic channel is not mass-producible: the non-standard logic union structure, non-trivial alignment necessary, unreliable layer bonding, and aforementioned fluidic disturbance all add to the difficulty of making real 3D microfluidic computing devices. As each specific logic function is realized by a specific structure; see for example [NPL 14], [NPL 11] and [NPL 25], a different logic output can only be accomplished by re-assembling various logic components, each time requiring different design(s), another round of fabrication, and dealing with potential fluidic turbulence problems in the new assembled structure. For example, [NPL 28] describes some active logic control, but also requires complex electrode array and extra control of the electrodes, while [NPL 5], [NPL 14] and [NPL 20] are passive control only and dependent on the structure, surface tension and flowrates in their respective microfludic chip(s).
Thus, an active control device instead of the known passive control devices, which rely on pressure difference and structure, is desired.
It is also desired that on-chip droplet control simplify the controlling scheme while preserving the inherent delicacy of micro-devices. It is also desired that the microfluidic computing devices be “smart” enough to “think” by themselves, i.e. the outputs should fully depend on inputs in assigned tasks; see [NPL 7]. Researchers have demonstrated this possibility in both stream regulation method; see [NPL 14], [NPL 11] and [NPL 25], and bubble/droplets schemes; see [NPL 14] and [NPL 5]. Considering the digitalized microfluid, in which picoliter droplets are used as miniaturized reactors, the existence or absence of an “information” droplet can be a very good equivalent of binary 1 or 0. Moreover, the color, volume and component of droplets comprise other dimensions of information. Therefore, droplet-based microfluid logic devices which can self-feedback and can be cascaded to exhibit their own advantages in device-embedded fluidic control and computing are desired.
The following subject matter avoids round-trip fluidic manipulation, while realizing automatic response and logic manipulation and re-programmable hybrid circuitry. It is compatible with existing microfluidic and electronic technology and provides standardized device architecture for large scale integration. In contrast to the PTL references, the instant subject matter provides an active control device, and has a feedback loop for automatic droplet control. Furthermore, the droplet information can also be converted to electric signal for detection and other control. Accordingly, the electric circuit and microfluidic channel are truly combined, with the latter acting as an adjustable part in the circuit.
The automatic droplet logic manipulation discussed herein is realized by a “hybrid divider” structure to employ droplet(s) as a hybrid electronic component for actuator control. The hybrid divider can be a fundamental liquid-electronic hybrid rheostat, a hybrid voltage divider and related hybrid processor. It may be understood as a fluidic diode realized by voltage divider in fluidic form, with transferable circuit principles and the simplest architecture or structure to date. By introducing the hybrid divider, a new branch of fully automatic droplet logic control has been invented: the droplet logic gate. The traditional round-trip computer command controlling valves or droplets (in EWOD) is replaced by reprogrammable fluidic framework, and the fluidic output fully depends on the input, thereby realizing droplet-controlled microfluidic logic (on-chip droplet control); see for example [NPL 23]. Existing fluidic logic gate technologies contain distinct chip shape(s) for each specific logic function, limiting their applications. Fluidic channels could not be rearranged to realize another function in the same chip. Instead, another chip must be fabricated for the task, i.e. ten chips for ten tasks. In contrast, the hybrid divider discussed herein is reprogrammable by voltage, i.e. one chip/processor for every task, like a fluidic CPU.
Introduction of droplet(s) to electronic circuit(s), or conversely, introduction of electronic switch(es)/actuator(s) as a component of fluidic circuitry is described for various combinations and applications. Thus, fast and automatic logic control of droplet(s) is achieved. Furthermore, real problems can be solved by integration of the fluidic hybrid diode as described: as a fluidic processor programmed by voltage signal and responsive to fluidic input, i.e. its fluidic output depends on its fluidic input.